Generation of viable cell active biomaterial patterns by laser transfer

ABSTRACT

A method for depositing a transfer material onto a receiving substrate uses a source of laser energy, a receiving substrate, and a target substrate. The target substrate comprises a laser-transparent support having a laser-facing surface and a support surface. The target substrate also comprises a composite material having a back surface in contact with the support surface and a front surface. The composite material comprises a mixture of the transfer material to be deposited and a matrix material. The matrix material is a material that has the property that, when it is exposed to laser energy, it desorbs from the laser-transparent support. The source of laser energy is positioned in relation to the target substrate so that laser energy is directed through the laser-facing surface of the target substrate and through the laser-transparent support to strike the composite material at a defined target location. The receiving substrate is positioned in a spaced relation to the target substrate. The source of laser energy has sufficient energy to desorb the composite material at the defined target location, causing the composite material to desorb from the defined target location and be lifted from the support surface of the laser-transparent support. The composite material is deposited at a defined receiving location on the receiving substrate. The method is useful for creating a pattern of biomaterial on the receiving substrate.

[0001] This nonprovisional application is a continuation-in-partapplication of U.S. patent application Ser. No. 09/671,166 filed on Sep.28, 2000, which is a divisional application of U.S. Pat. No. 6,177,151filed on May 25, 1999, which claims benefit of U.S. provisional patentapplication No. 60/117,468 filed on Jan. 27, 1999. This application alsoclaims benefit of U.S. provisional patent application No. 60/269,384filed on Feb. 20, 2001 as to certain matter. All applications andpatents named above are incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The invention relates generally to a method for the deposition ofmaterials and more specifically to a method for direct writing of a widerange of different biomaterials onto a substrate.

[0004] 2. Description of the Prior Art

[0005] The term “direct write” refers generally to any technique forcreating a pattern directly on a substrate, either by adding or removingmaterial from the substrate, without the use of a mask or preexistingform. Direct write technologies have been developed in response to aneed in the electronics industry for a means to rapidly prototypepassive circuit elements on various substrates, especially in themesoscopic regime, that is, electronic devices that straddle the sizerange between conventional microelectronics (sub-micron-range) andtraditional surface mount components (10+ mm-range). (Direct writing mayalso be accomplished in the sub-micron range using electron beams orfocused ion beams, but these techniques, because of their small scale,are not appropriate for large-scale rapid prototyping.) Direct writingallows for circuits to be prototyped without iterations inphotolithographic mask design and allows the rapid evaluation of theperformance of circuits too difficult to accurately model. Further,direct writing allows for the size of printed circuit boards and otherstructures to be reduced by allowing passive circuit elements to beconformably incorporated into the structure. Direct writing methods fortransferring electronic materials can also be useful for transferringbiomaterials to make simple or complex biomaterial structures, with orwithout associated electronic circuitry. Direct writing can becontrolled with CAD/CAM programs, thereby allowing electronic circuitsto be fabricated by machinery operated by unskilled personnel orallowing designers to move quickly from a design to a working prototype.Mesoscopic direct write technologies have the potential to enable newcapabilities to produce next generation applications in the mesoscopicregime.

[0006] Currently known direct write technologies for adding materials toa substrate include ink jet printing, Micropen® laser chemical vapordeposition (LCVD), laser particle guidance (Optomec, Inc.), and laserengineered nano-shaping (LENS). Currently known direct writetechnologies for removing material from a substrate include lasermachining, laser trimming and laser drilling.

[0007] The direct writing techniques of ink jet printing, screening, andMicropen® are wet techniques, that is, the material to be deposited iscombined with a solvent or binder and is squirted onto a substrate. Thesolvent or binder must later be removed by a drying or curing process,which limits the flexibility and capability of these approaches. Inaddition, wet techniques are inherently limited by viscoelasticproperties of the fluid in which the particles are suspended ordissolved.

[0008] In the direct writing technique known as “laser induced forwardtransfer” (LIFT), a pulsed laser beam is directed through alaser-transparent target substrate to strike a film of material coatedon the opposite side of the target substrate. The laser vaporizes thefilm material as it absorbs the laser radiation and, due to the transferof momentum, the material is removed from the target substrate and isredeposited on a receiving substrate that is placed in proximity to thetarget substrate. Laser induced forward transfer is typically used totransfer opaque thin films, typically metals, from a pre-coated lasertransparent support, typically glass, SiO₂, Al₂O₃, SrTiO₃, etc., to thereceiving substrate. Various methods of laser-induced forward transferare described in, for example, the following U.S. patents andpublications incorporated herein by reference: U.S. Pat. No. 4,752,455to Mayer, U.S. Pat. No. 4,895,735 to Cook, U.S. Pat. No. 5,725,706 toThoma et al., U.S. Pat. No. 5,292,559 to Joyce, Jr. et al., U.S. Pat.No. 5,492,861 to Opower, U.S. Pat. No. 5,725,914 to Opower, U.S. Pat.No. 5,736,464 to Opower, U.S. Pat. No. 4,970,196 to Kim et al., U.S.Pat. No. 5,173,441 to Yu et al., and Bohandy et al., “Metal Depositionfrom a Supported Metal Film Using an Excimer Laser, J. Appl. Phys. 60(4) Aug. 15, 1986, pp 1538-1539. Because the film material is vaporizedby the action of the laser, laser induced forward transfer is inherentlya homogeneous, pyrrolytic technique and typically cannot be used todeposit complex crystalline, multi-component materials or materials thathave a crystallization temperature well above room temperature becausethe resulting deposited material will be a weakly adherent amorphouscoating. Moreover, because the material to be transferred is vaporized,it becomes more reactive and can more easily become degraded, oxidized,or contaminated. The method is not well suited for the transfer oforganic materials, since many organic materials are fragile, thermallylabile, and can be irreversibly damaged during deposition. Moreover,functional groups on an organic polymer can be irreversibly damaged bydirect exposure to laser energy. Neither is the method well suited forthe transfer of biomaterials. The cells or biomolecules can be damagedduring deposition. Other disadvantages of the laser induced forwardtransfer technique include poor uniformity, morphology, adhesion, andresolution. Further, because of the high temperatures involved in theprocess, there is a danger of ablation or sputtering of the support,which can cause the incorporation of impurities in the material that isdeposited on the receiving substrate. Another disadvantage of laserinduced forward transfer is that it typically requires that the coatingof the material to be transferred be a thin coating, generally less that1 μm thick. Because of this requirement, it is very time-consuming totransfer more than very small amounts of material.

[0009] In a simple variation of the laser induced forward depositiontechnique, the target substrate is coated with several layers ofmaterials. The outermost layer, that is, the layer closest to thereceiving substrate, consists of the material to be deposited and theinnermost layer consists of a material that absorbs laser energy andbecomes vaporized, causing the outermost layer to be propelled againstthe receiving substrate. Variations of this technique are described in,for example, the following U.S. patents and publications incorporatedherein by reference: U.S. Pat. No. 5,171,650 to Ellis et al., U.S. Pat.No. 5,256,506 to Ellis et al., U.S. Pat. No. 4,987,006 to Williams etal., U.S. Pat. No. 5,156,938 to Foley et al. and Tolbert et al., “LaserAblation Transfer Imaging Using Picosecond Optical pulses: Ultra-HighSpeed, Lower Threshold and High Resolution” Journal of imaging Scienceand Technology, Vol.37, No.5, Sept./Oct. 1993 pp.485-489. A disadvantageof this method is that, because of the multiple layers, it is difficultor impossible to achieve the high degree of homogeneity of depositedmaterial on the receiving substrate required, for example, for theconstruction of electronic devices, sensing devices or passivationcoatings.

[0010] U.S. Pat. No. 6,177,151 to Chrisey et al. discloses the MAPLE-DW(Matrix Assisted Pulsed Laser Evaporation Direct Write) method andapparatus. The method comprises the use of laser energy to cause acomposite material to volatilize, desorb from a laser-transparentsupport, and be deposited on a receiving substrate. The compositematerial comprises a matrix material and a transfer material. Thetransfer material is the material desired to be transferred to thereceiving substrate. The matrix material is more volatile than thetransfer material and binds the transfer material into the compositematerial. The laser energy causes the matrix material to volatilize andpropel the transfer material onto the receiving substrate. Theproperties of the transfer material are preserved after deposition. Thismethod will be further described in the Detailed Description of thePreferred Embodiments below.

[0011] U.S. Pat. No. 6,177,151 is primarily directed to the transfer ofelectronic materials to form circuitry on the receiving substrate. Italso discloses the transfer of chemoselective materials and bioselectivematerials. Examples of biochemical materials disclosed include proteins,oligopeptides, polypeptides, whole cells, biological tissue, enzymes,cofactors, nucleic acids, DNA, RNA, antibodies (intact primary,polyclonal, and monoclonal), antigens, oligosaccharides,polysaccharides, oligonucleotides, lectins, biotin, streptavidin, andlipids. The prior art does not disclose MAPLE-DW transfer of living oractive biomaterials.

[0012] There is need for a method for transferring living or activebiomaterials in such a way that desired properties of the biomaterialsare preserved. The biomaterials should remain living or active afterdeposition onto the receiving substrate. Such a method would be usefulto generate micron-scale patterns of living cells and activebiomaterials for next generation 3-D tissue engineering, fabrication ofcell, protein, or antibody-based microfluidic biosensor arrays, andselective separation and culturing of microorganisms. There is also aneed for a method to micromachine away portions of a receiving substrateand or deposited transfer material using the same laser-transferapparatus.

SUMMARY OF THE INVENTION

[0013] It is an object of the invention to provide methods fordepositing a transfer material on a receiving substrate wherein apattern of deposited composite material can be created directly on thereceiving substrate without the use of a mask.

[0014] It is a further object of the invention to provide a method thatis useful for depositing a wide range of transfer materials includingliving or active biomaterials with no damage to the transfer material.

[0015] It is a further object of the invention to provide a method fordepositing a transfer material on a receiving substrate at ambientconditions.

[0016] It is a further object of the present invention to provide amethod for depositing a transfer material on a receiving substrate bylaser induced deposition wherein the spatial resolution of the depositedcomposite material can be as small as 1 μm.

[0017] It is a further object of the invention to provide a method fordepositing transfer materials on a receiving substrate in a controlledmanner wherein the process can be computer-controlled.

[0018] It is a further object of the invention to provide a method fordepositing transfer materials on a receiving substrate in a controlledmanner wherein it is possible to switch rapidly between differenttransfer materials to be deposited on the receiving substrate.

[0019] It is a further object of the invention to provide a method tomicromachine away a portion of a receiving substrate or depositedcomposite material.

[0020] These and other objects of the invention are accomplished by amethod for laser deposition comprising the steps of: providing one ormore sources of laser energy that produce laser energy; providing areceiving substrate; wherein the receiving substrate is positionedopposite the source of laser energy; providing a target substrate;wherein the target substrate is positioned between the receivingsubstrate and the source of laser energy; wherein the target substratecomprises a laser-transparent support and a composite material; whereinthe laser-transparent support has a laser-facing surface facing thesource of laser energy; wherein the laser-transparent support has asupport surface facing the receiving substrate; wherein the compositematerial has a back surface in contact with the support surface; whereinthe composite material has a front surface facing the receivingsubstrate; wherein the composite material comprises a matrix materialand a transfer material; and wherein the matrix material has theproperty of being desorbed from the laser-transparent support whenexposed to the laser energy; positioning the source of laser energy in aspaced relation to the target substrate so that the laser energy willstrike the composite material at a defined target location; positioningthe receiving substrate in a spaced relation to the target substrate;and exposing the target substrate to the laser energy; wherein the laserenergy is directed through the laser-facing surface and through thelaser-transparent support to strike the composite material at thesupport surface-back surface interface at a defined target location;wherein the laser energy has sufficient energy to cause the desorptionof the composite material from the support surface; and wherein thedesorbed composite material is deposited at a defined receiving locationon the receiving substrate to form a deposited composite material.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021]FIG. 1a is a schematic representation of a MAPLE-DW apparatus whenused to transfer composite material 16 to a receiving substrate 18.

[0022]FIG. 1b is a schematic representation of the MAPLE-DW apparatuswhen used to micromachine away a portion of the receiving substrate 18.

[0023]FIGS. 2a and 2 b are schematic representations of thelaser-transparent support 15, the composite material 16, and thereceiving substrate 18 before (2 a) and after (2 b) the depositing ofthe composite material 16 on the receiving substrate 18 to form adeposited composite material 26.

[0024]FIGS. 3a and 3 b are schematic representations of a definedmachining location 28 on a receiving substrate 18 (3 a) made using theapparatus of FIG. 1b, and a deposited composite material 26 in a definedmachining location 28 (3 b) made using the apparatus of FIG. 1a.

[0025]FIG. 4 is a detailed schematic representation of a targetsubstrate 17 with a laser-absorbing layer 19, also showing thelaser-transparent support 15, composite material 16, laser-facingsurface 30, support surface 32, back surface 34, and front surface 34.LIST OF REFERENCE NUMBERS 12 source of laser energy 14 laser energy 15laser-transparent support 16 composite material 17 target substrate 18receiving substrate 19 laser-absorbing layer 20 laser positioning means22 target substrate positioning means 24 receiving substrate positioningmeans 26 deposited composite material 28 defined machining location 30laser-facing surface 32 support surface 34 back surface 36 front surface

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026]FIG. 1a schematically illustrates a MAPLE-DW apparatus used in thepresent invention. The apparatus includes a source of laser energy 12that produces laser energy 14, a target substrate 17, and a receivingsubstrate 18. The receiving substrate 18 is positioned opposite thesource of laser energy 12. The target substrate 17 is positioned betweenthe receiving substrate 18 and the source of laser energy 12. FIG. 4schematically illustrates the target substrate in detail. The targetsubstrate 17 comprises two layers: a laser-transparent support 15 and acomposite material 16. The laser-transparent support 15 has alaser-facing surface 30 that faces the source of laser energy 12 and asupport surface 32 that faces the receiving substrate 18. The compositematerial 16 has a back surface 34 in contact with the support surface 32and a front surface 36 facing the receiving substrate 18. The compositematerial 16 comprises a matrix material and a transfer material. Thematrix material has the property of being desorbed from thelaser-transparent support 15 when exposed to the laser energy 14.

[0027] The method of the invention for laser deposition comprises thesteps of: providing one or more sources of laser energy 12 that producelaser energy 14, providing a receiving substrate 18, providing a targetsubstrate 17, positioning the source of laser energy 12, positioning thereceiving substrate 18, and exposing the target substrate 17. In thestep of positioning the source of laser energy 12, the source of laserenergy 12 is positioned in a spaced relation to the target substrate 17so that the laser energy 14 will strike the composite material 16 at adefined target location. In the step of positioning the receivingsubstrate, the receiving substrate 18 is positioned in a spaced relationto the target substrate 17. In the step of exposing the target substrate17, laser energy 14 from the source of laser energy 12 is directedthrough the laser-facing surface 30 and through the laser-transparentsupport 15 to strike the composite material 16 at the supportsurface-back surface 32, 34 interface at a defined target location. Thelaser energy 14 has sufficient energy to cause the desorption of thecomposite material 16 from the support surface 32. The desorbedcomposite material is deposited at a defined receiving location on thereceiving substrate 18 to form a deposited composite material 26. Unlessotherwise stated, all steps can be performed in any sequence thatresults in a deposited composite material 26 on the receiving substrate18. Preferably, the method is controlled by a computer.

[0028] Preferable, the method is carried out at about room temperatureand about atmospheric pressure. The method can also be carried out underone or more controlled conditions selected from the group consisting ofhumidity, atmospheric composition, air pressure, temperature, andsterility.

[0029]FIGS. 2a and 2 b schematically illustrate the effects of exposingthe composite material 16 to the laser energy 14, whereby the compositematerial 16 desorbs from the surface of the target substrate 17 so thatthe composite material 16 is deposited onto the receiving substrate 18forming the deposited composite material 26.

[0030] Any suitable source of laser energy may be used in the presentinvention. In general, a pulsed laser is preferred. (As used herein, theterms “laser” and “source of laser energy” are used interchangeably torefer to any device that creates a laser beam.) A pulsed laser has theadvantage of generating a very short burst of laser energy 14 thatprevents damage to the composite material 16. Lasers for use inaccordance with the present invention can be any type such as aregenerally used with other types of laser deposition. Pulsed lasers arecommercially available within the full spectral range from UV to IR.Typically, such lasers emit light having a wavelength in the range ofabout 157 nm-1100 nm, an energy density of about 0.05-10 J/cm²(typically about 0.1-2.0 J/cm²), a pulsewidth of about 10⁻¹²10⁻⁶ secondand a pulse repetition frequency of about 0 to greater than 20,000 Hz.In general, energy density (fluence) affects the morphology of thedeposited composite material 26; higher energies tend to producedeposited composite material 26 that have larger particles. Examples ofsuitable lasers include, but are not limited to, pulsed gas lasers suchas excimer lasers, i.e. F₂ (157 nm), ArF (193 nm), KrF (248 nm). XeCl(308 nm), XeF (351 μm), CO₂, nitrogen, metal vapor, etc.; pulsed solidstate lasers such as Nd:YAG, Ti:Sapphire, Ruby, diode pumped,semiconductor, etc.; and pulsed dye laser systems. Typically, theparticular laser is selected with regard to the energy needed to desorbthe composite material 16 from the support surface 32. Some embodimentsof the method use a matrix material that comprises water. In thosecases, an ArF excimer laser (193 nm) is suitable, because the water willabsorb that wavelength of laser energy 14. The energy density should behigh enough to desorb the composite material, but not so high that thelaser energy 14 damages the transfer material. When the transfermaterial is a biomaterial, a typical range of energy density is about 50to about 200 mJ/cm². However, higher energy densities are sometimespossible.

[0031] The dimensions of the laser energy 14 can be controlled by anymeans known in the art so that only a precisely defined area of thetarget substrate 17 is exposed to the laser energy 14 and so that only aprecisely defined portion of the composite material 16 desorbs. Thelaser energy 14 can be focussed through an objective to narrow the beamand desorb a smaller portion of composite material 16. This increasesthe possible resolution of the deposited composite material 26. It ispossible to focus the laser energy 14 so that it is small enough totransfer a single cell to the receiving substrate 18 from a compositematerial 16 containing a cluster of cells. Single cell transfers canalso be achieved by using a very dilute concentration of cells in thecomposite material 16.

[0032] The receiving substrate 18 should be positioned so that when thecomposite material 16 on the laser-transparent support 15 is desorbed,the composite material 16 can be deposited at a defined receivinglocation on the receiving substrate 18. Also, there should be enoughspace between the target substrate 17 and the receiving substrate 18 sothat volatilized matrix material, or byproducts from laser-induceddecomposition of the matrix material, can escape from the space betweenthe target substrate 17 and the receiving substrate 18. Preferably, thereceiving substrate 18 is positioned about 10 to about 100 μm from thesurface of the composite material 16.

[0033] The laser 12, target substrate 17, and the receiving substrate 18should be moveable with respect to each other so that the compositematerial 16 can be deposited in a pattern and so that after thecomposite material 16 desorbs at one defined target location on thetarget substrate 17, the laser energy 14 can be directed to anotherdefined target location on the target substrate 17 where the compositematerial 16 has not yet desorbed. For example, to deposit a line ofcomposite material 16 on the receiving substrate 18, the laser 12 ismoved with respect to the target substrate 17 and the receivingsubstrate 18, which may be held stationary with respect to each other.As the laser 12 moves with respect to the substrates, it directs laserenergy 14 to a new defined target location on the target substrate 17where the composite material 16 has not yet desorbed, and causes thecomposite material 16 to be deposited onto a new defined receivinglocation on the receiving substrate 18. The successive defined receivinglocation may overlap to the extent necessary to create a continuous lineof deposited composite material 26 on the receiving substrate 18.

[0034] To increase the thickness of deposited composite material 26 at aparticular defined receiving location, the laser 12 and the receivingsubstrate 18 are held stationary with respect to each other and thetarget substrate 17 is moved with respect to the laser 12 and thereceiving substrate 18. The laser energy 14 is directed to a new definedtarget location on the target substrate 17 where the composite material16 has not yet desorbed. The composite material 16 is deposited onto thesame defined receiving location on the receiving substrate 18 in anincreasingly thickened deposit. (As used herein, the terms “moving [a]with respect to [b]” or “moving [a] and [b] with respect to each other”mean that either [a] or [b] can be moved to effect a change in theirrelative position.)

[0035] The steps of positioning the source of laser energy 12 andpositioning the receiving substrate 18 can be achieved through the useof one or more positioning means selected from the group consisting of alaser positioning means 20, a target substrate positioning means 22, anda receiving substrate positioning means 24. These positioning means canbe any positioning means known in the art for supporting a source oflaser energy 12, a target substrate 17, and a receiving substrate 18 andmoving them in a controlled and defined manner. For example, similarpositioning means and moving means for a laser, target and receivingsubstrate are known in the fields of laser transfer deposition and laserinduced forward transfer. The laser 12 may be positioned in any locationthat provides an optical path between the laser 12 and the targetsubstrate 17 so that sufficient laser energy 14 can be directed todefined target locations on the target substrate 17. It is not alwaysnecessary to use all three positioning means. It is only necessary tocontrol the relative positions of the components such that the laserenergy 14 strikes the target substrate 17 at the desired defined targetlocation, and the desorbed composite material 16 lands on the receivingsubstrate 18 at the desired defined receiving location.

[0036] Many embodiments of the general method are possible. Thecomposite material can be deposited in a two-dimensional pattern or athree-dimensional pattern of deposited composite material 26. This doneby repeating the steps of positioning the source of laser energy,exposing the target substrate 17, and positioning the receivingsubstrate at successive defined target locations and successive definedreceiving locations. This creates multiple instances of depositedcomposite material 26 that can be positioned in any two-dimensionalpattern or three-dimensional pattern desired. A three-dimensionalpattern can be created by placing deposited composite material 26 on topof deposited composite material 26 already on the receiving substrate18.

[0037] The method can also be used to micromachine away portions of thereceiving substrate 18. This can be done before the step of providing atarget substrate 17 by positioning the receiving substrate 18 in aspaced relation to the source of laser energy 12, and exposing thereceiving substrate 18 to the laser energy 14 so that the laser energy14 machines away a defined machining location 28 on the receivingsubstrate 18. FIG. 1b schematically illustrates the apparatus used tocarry out this method. The laser energy 14 directly strikes thereceiving substrate 18 without a target substrate 17 in between. Thiscan be done with the same source of laser energy 12 as is used fordesorbing the composite material 16, or a different one. FIG. 3aschematically illustrates the resulting defined machining location 28 onthe receiving substrate 18.

[0038] Another embodiment can be used to micromachine away portions ofthe deposited composite material 26 and the receiving substrate 18. Thiscan be done after the steps of exposing the target substrate 17 andpositioning the receiving substrate by removing the target substrate 17from its position between the source of laser energy 12 and thereceiving substrate 18, positioning the receiving substrate 18 in aspaced relation to the source of laser energy 12, and exposing thereceiving substrate 18 to the laser energy 14 so that the laser energy14 machines away a defined machining location 28 on the receivingsubstrate 18 or on the deposited composite material 26. This isessentially the same method as above except that it occurs after thedeposited composite material 26 is on the receiving substrate 18.

[0039] The above micromachining methods can also be used to micromachinea via, or small hole, all the way through the receiving substrate 18.Micromachining is also useful for creating channels in the receivingsubstrate 18 and for removing excess deposited composite material 26. Inanother embodiment, the composite material 16 is deposited directly intoa defined machining location 28 already micromachined away by the laserenergy 14. FIG. 3b schematically illustrates the resulting depositedcomposite material 26 in a defined machining location 28 on thereceiving substrate 18.

[0040] In another embodiment the step of providing a target substrate 17is repeated one or more times using target substrates 17 comprisingdifferent composite materials 16. The different composite materials 16are deposited in respective patterns on the receiving substrate 18. Withthis method two or more composite materials 16 can be combined on onereceiving substrate 18 in any desired combination of patterns. Theapparatus of the present invention can be adapted so that a plurality ofdifferent composite materials 16 can be deposited consecutively onto areceiving substrate 18 by providing a way to consecutively move eachtarget substrate 17 into a position for depositing material from aparticular target substrate 17 onto the receiving substrate 18.Consecutive deposition of different composite materials 16 can also beaccomplished by providing a target substrate 17 that is subdivided intoa plurality of different subregions that each have a different compositematerial 16 and providing a way to select a particular subregion anddeposit the composite material 16 from that subregion onto the receivingsubstrate 18. The different composite materials 16 can comprisedifferent transfer materials. This allows the deposition ofmulti-component structures on the receiving substrate 18.

[0041] The laser-transparent support 15 is typically planar, having asupport surface 32 that is coated with the composite material 16 and alaser-facing surface 30 that can be positioned so that the laser energy14 can be directed through the laser-transparent support 15. Thecomposition of the laser-transparent support 15 is selected inaccordance with the particular type of laser that is used. For example,if the laser 12 is a pulsed UV laser, the laser-transparent support 15may be an UV-transparent material including but not limited to quartz ormachine etched quartz. If the laser 12 is an IR laser, thelaser-transparent support 15 may be an IR-transparent materialincluding, but not limited to plastic, silicon, fused silica, orsapphire. Similarly, if the laser 12 is a visible laser, thelaser-transparent support 15 may be a material that is transparent inthe visible range, including, but not limited to soda lime andborosilicate glasses. A laser-transparent flexible polymer ribbon canalso be a suitable laser-transparent support 15.

[0042] The support surface 32 of the laser-transparent support 15 canfurther comprise a laser-absorbing layer 19 in contact with the backsurface 34 of the composite material 16. This is schematicallyillustrated in FIG. 4. The laser-absorbing layer 19 absorbs the laserenergy 14 and vaporizes at the site of absorption. The vaporization aidsin the desorption of the composite material 16 from thelaser-transparent support 15 and propels the composite material 16towards the receiving substrate 18. The use of a laser-absorbing layer19 can result in a cleaner desorption with less damage to the transfermaterial and a higher resolution. A suitable laser-absorbing layer 19can comprise one or more materials selected from the group consisting ofgold, chrome, and titanium.

[0043] The receiving substrate 18 can be any solid material, planar ornon-planar, onto which one may wish to deposit the composite material16. The receiving substrate 18 can comprise one or more materialsselected from the group consisting of chemically functionalized glass,polymer-coated glass, quartz, natural hydrogel, synthetic hydrogel,uncoated glass, nitrocellulose coated glass, silicon, glass, plastics,metals, and ceramics. The receiving substrate 18 can comprisefunctionalization that interacts with the deposited composite material26. The functionalization is selected from the group consisting ofcovalent functionalization, physisorbed functionalization, andcombinations thereof. Surfaces with functionalization can be prepared byany method known in the art. Surfaces with functionalization can alsooccur naturally, such as a living host. Covalent functionalization iswhen the deposited composite material 26 becomes covalently bonded tothe surface of the receiving substrate 18. Physisorbed functionalizationis when the deposited composite material 26 becomes attached or adsorbedto the receiving substrate 18 by means other than covalent bonding.Examples of functionalization include a living host, a living cell, aliving cell culture, a non-living cell, a non-living group of cells, aliving tissue, a chemically functionalized surface, and a biologicallyfunctionalized surface.

[0044] The composite material 16 comprises a matrix material and atransfer material. The transfer material is any functional material ofinterest to be transferred to the receiving substrate 18 that one maywish to deposit on a substrate in a defined pattern. The purposes of thematrix material are to protect the transfer material from the laserenergy and to allow desorption of the composite material 16 from thelaser-transparent support 15. The composite material 16 can be a solid,a liquid, or a theological fluid, although liquids are not preferred.

[0045] The transfer material can be any biomaterial. The biomaterial canbe in its living or active state. An active biomaterial is one that iscapable of performing its natural or intended biological function.Suitable biomaterials can comprise any of the following examples, butare not limited to these examples:

[0046] Proteins, hormones, enzymes, antibodies, DNA, portions of DNAstrands, inorganic nutrients, aqueous salt solutions, RNA, nucleicacids, aptamers, antigens, lipids, oligopeptides, polypeptides,cofactors, and polysaccharides.

[0047] A single cell, groups of cells, living cells, multi-cellassemblies, pluripotent cells, stem cells, heart cells, lung cells,muscle cells neurons, and neural networks.

[0048] Living tissue, skin, hair-producing tissue, nail-producingtissue, and brain tissue.

[0049] DNA-coated particles, protein-coated particles, and RNA-coatedparticles.

[0050] Functional supporting media such as nutrients and other lifesupporting material.

[0051] Organic tagging compounds and inorganic tagging compounds. Atagging compound is a compound that allows for the detection of thedeposited composite material 26. This can be done to verify the correctplacement of the deposited composite material 26 and to verify that thebiomaterial is still living or active.

[0052] When more than one composite materials 16 is used, one or more ofthem can comprise a transfer material comprising an electronic transfermaterial. The electronic transfer material is used to create electroniccircuitry on the receiving substrate 18. The electronic transfermaterial can be independently selected from the group consisting ofmetal, dielectric, resist, semiconductor, and combinations thereof.These methods for creating circuitry are described in detail in U.S.Pat. No. 6,177,151. The circuitry can be designed to interact with adeposited composite material 26 that comprises biomaterial.

[0053] It is the presence of the matrix material that provides theadvantages that the present invention has over methods such as laserinduced forward transfer (LIFT). The matrix material is selectedprimarily according to two criteria: the matrix material must becompatible with the transfer material so that the matrix material andthe transfer material can be combined into a mixture to form thecomposite material 16 on the support surface 32 of the laser-transparentsupport 15, and the matrix material must have the property of beingdesorbed from the laser-transparent support 15 when exposed to laserenergy 14. When the composite material 16 is exposed to the laser energy14, the matrix material may evaporate via electronic and vibrationalexcitation. The evaporated interfacial layers of matrix material thenrelease the remaining composite material 16 so that the compositematerial 16 desorbs from the support surface 32 of the laser-transparentsupport 15 and moves toward the receiving substrate 18. The amount ofmatrix material that is used in the composite material 16 relative tothe amount of the transfer material can be any amount sufficient toaccomplish the purposes described above. Typically, the amount will varyaccording to the particular matrix material and transfer material.

[0054] Suitable matrix materials can comprise any of the followingexamples, but are not limited to these examples: glycerol, water,polymer, cell medium, cell nutrient, natural hydrogel, synthetichydrogel, surfactant, antibiotic, antibody, antigen, protein,dimethylsulfoxide, water/dimethylsulfoxide mixture, agarose, salinesolution, dielectric particles, metal particles, aqueous inorganic saltsolution, nitrocellulose gel, sol gel, ceramic composite, DNA-coatedparticles, protein-coated particles, and RNA-coated particles.

[0055] An important property of the matrix material is its ability tomaintain the biomaterial in a living or active state. Such matrixmaterials appropriate for various biomaterials are known in the art.Other factors that can be taken into account in selecting the optimummatrix material to go with a particular transfer material include theability of the matrix material to form a colloidal or particulatesuspension with the particular transfer material, the melting point,heat capacity, molecular size, chemical composition, spectral absorptioncharacteristics and heat of vaporization of the matrix material (factorsthat affect the ability of the matrix material to desorb and lift thetransfer material from the laser-transparent support 15) and thereactivity or nonreactivity of the matrix material towards the transfermaterial.

[0056] The matrix material may also serve other functions. For example,the matrix material may help prevent the transfer material from bindingtoo tightly to the laser-transparent support 15. At the same time, thepresence of the matrix material may aid in the construction of thecomposite material 16 on the laser-transparent support 15 by helping tohold the transfer material in place on the laser-transparent support 15,especially if the transfer material is a powder. This can sometimes beachieved by freezing the composite material 16 to the laser-transparentsupport 15 if the composite material 16 is a liquid at room temperature.The composite material 16 may be coated onto the support surface 32 ofthe laser-transparent support 15 and then the composite material 16 maybe frozen to form a solid coating. The target substrate 17 may be keptfrozen while the composite material 16 is being exposed to the laserenergy 14 during the deposition process. The rest of the apparatus neednot be kept frozen during the deposition process.

[0057] Freezing is appropriate when the matrix material comprises awater/glycerol solution or a water/dimethylsulfoxide solution. Thefreezing temperature for some composite materials 16 may be in the rangefrom about −50° C. to about 100° C. The composite material 16 may alsobe held at the incubation temperature of the biomaterial to assist inkeeping the biomaterial in its living or active state.

[0058] Another consideration is any special ability a particular matrixmaterial may have to impart protection to a particular transfer materialfrom damage during the lasing, desorption, and transfer to the receivingsubstrate 18. For example, a matrix material that absorbs laser energy14 at the same wavelength as an important functional group on thetransfer material may serve to protect the transfer material from damagefrom exposure to the laser energy 14. Alternatively, a matrix materialmay be used that absorbs at a wavelength in a spectral regionsubstantially outside that of the transfer material. In this instance,the matrix material transforms laser energy into kinetic energy, and thekinetic energy is imparted to the transfer material. Examples of matrixmaterials include but are not limited to addition polymers (see below),condensation polymers (see below), photoresist polymers (see below),water, glycerol, dimethylsulfoxide, surfactant, aryl solvents,especially toluene, acetophenone and nicotinic acid, arene compounds(e.g. naphthalene, anthracene, phenanthrene), t-butylalcohol,halogenated organic solvent, hydrocarbons, ketones, alcohols, ethers,esters, carboxylic acids, phenols and phosphoric acid. It is alsoimportant sometimes to choose a matrix material that is a cushion forthe transferred material, absorbing some of the impact energy, andlimiting the damage to the transfer material.

[0059] The matrix material may also be a polymer that decomposes or“unzips” into volatile components when exposed to laser energy. Thevolatile decomposition products then act to propel or lift the transfermaterial off of the laser-transparent support 15. The polymeric matrixmaterial acts as a propellant and at room temperature the propellantproducts are volatilized away while the transfer material is depositedas a thin film on the receiving substrate.

[0060] Unzipping mechanisms are typically catalyzed by a photon that isabsorbed by the polymer and leads to chain cleavage, formation of a freeradical (The free radical can be formed either by a thermally drivenprocess or by a photochemical process) in the chain which then travelsdown the polymer chain leading to a chain unzipping that can produce themonomer species. The monomer, ejected at high kinetic energies, impartssome of this energy to the transfer material mixed with the polymer. Onegeneral controlling factor for depolymerization or unzipping of additionpolymers is the ceiling temperature of the polymer. At the ceilingtemperature, the rates of polymerization and depolymerization are equal.At temperatures above the ceiling temperature, depolymerizationdominates polymerization. Laser radiation allows the high ceilingtemperatures required for depolymerization to be reached betweenradiation pulses.

[0061] In general, polymeric propellants that are suitable candidatesfor consideration as matrix materials are taken from the class ofpolymers called addition polymers. As a subclass of addition polymers,the suitable candidate materials are typically sterically crowded andare generally thermally unstable. The general polymer classes that areof interest with known properties include poly(alkenes), poly(acrylics),poly(methacrylics), poly(vinyls), poly(vinylketones), poly(styrenes),poly (oxides), or polyethers. In general, addition polymers with alphasubstituted structures consistently exhibit lower ceiling temperaturesthan their unsubstituted parent species and are strong candidatematerials. Polymers from the class of materials called condensationpolymers, as well as the class of materials called photoresist polymers,may also have some utility, especially if they decompose to volatilematerials. The spectrum of candidate materials is wide and many polymerpropellants can be used as the matrix material. Not all will be ideal inall characteristics. For example, repolymerization of a polymeric matrixmaterial on the receiving substrate may be a problem with somematerials. Other factors to be considered in the selection of the matrixmaterial include the absorption of UV laser radiation, volatility ofnative propellant material, efficiency of the unzipping process,products of unzipping or decomposition and their volatilty/toxicity,kinetic energy imparted by the propellant, degree of repolymerization,inertness of binder material, inertness of unzipped or decomposedpropellant, cost, availability, purity, and processability with thematerial of interest to be deposited.

[0062] Specific polymeric matrix materials include, but are not limitedto, the following: polyacrylic acid-butyl ester, nitrocellulose,poly(methacrylic acid)-methyl ester (PMMA), poly(methacrylic acid)-nbutyl ester (PBMA), poly(methacrylic acid)-t butyl ester (PtBMA),polytetrafluoroethylene (PTFE), polyperfluoropropylene, poly N-vinylcarbazole, poly(methyl isopropenyl ketone), poly alphamethyl styrene,polyacrylic acid, polyvinylacetate, polyvinylacetate with zinc bromidepresent, poly(oxymethylene), phenol-formaldehyde positive photoresistresins, and photobleachable aromatic dyes.

[0063] The matrix material may also contain components that assist inthe bonding of the transfer material to the receiving substrate or thatassist in the bonding of particles of the transfer material to eachother after they are deposited on the receiving substrate.

[0064] The transfer material and the matrix material may be combined toform the composite material 16 on the support surface 32 of thelaser-transparent support 15 in any manner that is sufficient to carryout the purpose of the invention. If the transfer material is soluble tosome extent in the matrix material, the transfer material may bedissolved in the matrix material. Alternatively, if the transfermaterial is not soluble in a suitable solvent, the transfer material maybe mixed with a matrix material to form a colloidal or particulatesuspension or condensed phase. Still another alternative is to combinethe matrix material and the transfer material with a solvent thatvolatilizes after the mixture is applied to the laser-transparentsupport 15. Still another alternative is to have a layer of matrixmaterial, such as a hydrogel, between the transfer material and thelaser-transparent support 15 without mixing the matrix material and thetransfer material. The matrix material can also include soluble orinsoluble dopants, that is, additional compounds or materials that onemay wish to deposit onto the film.

[0065] The mixture of the transfer material and the matrix material maybe applied to the support surface 32 of the laser-transparent support 15by any method known in the art for creating uniform coatings on asurface, including, for example, by spin coating, ink jet deposition,jet vapor deposition, spin spray coating, aerosol spray deposition,electrophoretic deposition, pulsed laser deposition, matrix assistedpulsed laser evaporation, thermal evaporation, sol gel deposition,chemical vapor deposition, sedimentation and print screening. Typically,the mixture of the transfer material and the matrix material will beapplied to the support surface 32 of the laser-transparent support 15 toform a composite material 16 that is between about 0.1 μm and about 100μm in thickness. Preferably, the composite material 16 is greater thanabout 1 μm in thickness, and, most preferably, is between about 1 μm andabout 20 μm in thickness. The thicker the composite material 16, themore of the transfer material can be transferred at one time, which isan advantage of the present invention over laser transfer methods thatuse thin films. On the other hand, a composite material 16 that is toothick will not desorb when exposed to the pulsed laser.

[0066] The embodiments described above can be combined in many ways,allowing for the deposition of complex multi-layer, multi-componentstructures with a wide range of uses and applications. The examplesdemonstrate the capability of placing biomaterials (proteins, a cell, orgroup of cells) onto various surfaces in a computer-controlled fashionand on a 10's of micron scale. This ability allows the making of manystructures and devices that require cells or other biomaterials to beplaced in patterns or 3D shapes where there is microscopic structure.The following describes devices and their uses that could be made usingthe method of the invention. These descriptions of devices are notintended to limit the scope of the invention.

[0067] 1) Engineered cellular or composite structures for growth,repair, replacement, or improvement of tissue: Tissue is comprised ofprecisely organized cells and biomolecules. Live tissue can be builtfrom these components (using cells as bricks and biomolecules as mortar)by building complex cell structures in a computer-controlled manner. Aspecific goal would be to use this tissue to implant it in the body toheal or improve existing tissue.

[0068] 2) Living organs: Organs are even more complicated tissuestructures that perform specific life-sustaining functions in the body.They contain several types of cells and biomolecules but would beassembled the same as tissue discussed in 1).

[0069] 3) Device to investigate inter- and intracellular signaling:There are several ways to investigate cell signaling includingelectronic detection, fluorescent probes, and gene or proteinidentification (cells use these molecules to communicate). The methodallows the placement of cells on a detection platform. Specifically, todo electronic or protein identification, cells would be placed on anelectronic circuit or in close proximity to a protein identificationmicroarray.

[0070] 4) Living device to control or divert the flow of fluid throughmicrofluidic channels: Muscle and cardiac cells/tissue can be placedinto microchannels. By placing the cells in a computer-controlledmanner, a structure can be built that squeezes out fluid when all musclecells are forced to contract at the same time using electricalstimulation. Likewise, a dam could be constructed from muscle tissuethat could release or direct fluid down a microchannel depending onwhether it was relaxed or contracted.

[0071] 5) Living, miniature electrode: Neurons are essentially livingelectrodes that the brain and nervous system use to actuate functions inthe body. Arrays and Microsystems of natural/living “electrodes” can bemade by depositing subsystems of neurons.

[0072] 6) Neural network: Same as 5) except the neurons are deposited ina connected network so that signals can pass from one area to another.The neural network can also mimic the transmission of impulses of thebrain or nervous system by using computer-control and design to mimicstructures found in the brain or nervous system. Communication linesthat mimic the body's natural communications are also possible.

[0073] 7) Device to investigate cell aging: Same as 3) except with thegoal of detecting proteins or DNA corresponding to cell aging or death.

[0074] 8) Bridge to connect a nerve synapse: This is the same as 5) and6) but with the specific goal of repairing part of the natural nervoussystem inside the body.

[0075] 9) Biofilm: Biofilms are organized, natural living structuresthat show signs of intelligence, i.e. advanced communication,organization, and function. They are made mainly from bacteria andexcreted molecules, both of which can be deposited in patterns by themethod of the invention. The idea would be to make a biofilm found innature by constructing it from its basic components using computercontrolled laser deposition of those materials.

[0076] 10) Drug delivery system or coating: There are and will be newadvanced molecules for coating and delivering drugs. Many of theseclasses of materials such as proteins or synthetic polymers can bedeposited by the method of the invention. Films and structures of thesematerials can be made for improved drug coatings and delivery.

[0077] 11) Implantable drug delivery system: A miniature biochip system,where one part contains a sensing or detecting element to detect adisease or medical condition, and another part contains a drug releasefunction that is activated by the detection side, can be made by themethod of the invention. The sensing element would contain an array ofenzymes or antibodies sensitive to a variety of diseases or moleculescharacteristic of a disease. The drug delivery side would contain coateddrug particles and a microfluidic injector to inject the drugs into thebody.

[0078] 12) Chemical or biological sensing device to sense chemicals orbiomaterials: Bio- and chemical sensors rely upon active biomolecules orcells to sense the presence of a specific active molecule. The method ofthe invention can deposit these biomolecules and cells onto a detectionplatform (i.e. electronics, fluorescence, or magnetic) to make one ofthese devices.

[0079] 13) Implantable, biocompatible sensor/signaler device: Like 12)except for the detection of non-diseased states such as a war-fightermonitor (fatigue, stress, wound, etc.) or a chemical or biologicalwarfare agent.

[0080] Having described the invention, the following examples are givento illustrate specific applications of the invention. These specificexamples are not intended to limit the scope of the invention describedin this application.

EXAMPLE 1

[0081] Transfer of Living E. coli Bacteria From a Frozen Support

[0082] The transfer material was living E. coli cells. The matrixmaterial was Luria-Bertani (LB) broth and kanamycin (50 μg/ml). The spotsize was 0.09 cm² and the 193 nm energy density was 0.2 J/cm². Thecomposite material 16 was frozen to the laser-transparent support 15.SEM micrographs showed that there was no damage to the transferredcells.

EXAMPLE 2

[0083] Transfer of Living E. coli bacteria From a Room TemperatureSupport

[0084] The transfer material was living E. coli cells. The matrixmaterial was LB broth, agar, and kanamycin. The composite material 16was coated on the laser-transparent support 15 and kept at roomtemperature. The same laser parameters as above resulted in successfultransfer.

EXAMPLE 3

[0085] Transfer of Living E. coli Bacteria From a Room TemperatureSupport

[0086] The transfer material was living GFP marked E. coli cells. Thematrix material was LB broth, kanamycin, glycerin, and barium titanatenanoparticles. This transfer was performed with a different pulsed UVlaser at 355 nm, a spot size of 65 microns, and an energy density of 1J/cm². A SEM micrograph taken under UV light showed fluorescent activityin the transferred cells, proving that the cells were still living.

EXAMPLE 4

[0087] Transfer of Living Chinese Hamster Ovaries (CHO)

[0088] The transfer material was living Chinese hamster ovary cells. Thematrix material was a hydrogel (Matrigel Matrix) layered below theliving cells. The composite material 16 was kept at room temperature.This transfer was performed with 193 nm 30 ns laser pulses at an energydensity of 150 mJ/cm². SEM micrographs showed that the cells weresuccessfully transferred. Micrographs taken after three days after thetransfer showed that the transferred cells had grown and multiplied onthe receiving substrate 18.

EXAMPLE 5

[0089] Transfer of Active Horseradish Peroxidase (HRP) From a FrozenSupport

[0090] The transfer material was active HRP. The matrix material was PBSbuffer. The concentration of HRP in the composite material 16 was 0.05 gHRP/g buffer. The composite material 16 was frozen to thelaser-transparent support 15. The spot size was 0.09 cm² and the 193 nmenergy density was 0.2 J/cm. Comparison of FTIR spectra of transferredHRP and spin-dried HRP confirmed that the transferred HRP was stillactive.

EXAMPLE 6

[0091] Transfer of Active Horseradish Peroxidase (HRP) From a RoomTemperature Support

[0092] The transfer material was active HRP. The matrix material was PBSbuffer and a 2 micron thick layer of polyurethane coated on thelaser-transparent support 15. HRP/buffer solution dropped, spread, anddried on top of the polymer coating at an initial concentration of 0.05g HRP/g buffer. The spot size was 0.09 cm², and the 193 nm energydensity was 0.2 J/cm². A H₂O₂/DAB activity test showed that thetransferred HRP was still active.

EXAMPLE 7

[0093] Transfer of Living Human Osteoblasts From a Room TemperatureSupport

[0094] The transfer material was living human osteoblasts. The matrixmaterial was a hydrogel (Matrigel Matrix) layered below the livingcells. This transfer was performed with 193 nm 30 ns laser pulses at anenergy density of <20 mJ/cm². Green fluorescence after laser transferand 20 hours of culture indicated live cells and near 100% viability.

EXAMPLE 8

[0095] Transfer of Living Mouse Stem Cells (Pluripotent Cells) From aRoom Temperature Support

[0096] The transfer material was living mouse stem cells. The matrixmaterial was with a hydrogel (Matrigel Matrix) layered below the livingcells. This transfer was performed with 193 nm 30 ns laser pulses at anenergy density of <20 mJ/cm². Green fluorescence after laser transferand 3 days of culture indicated live cells and near 100% viability.

We claim:
 1. A method for laser deposition comprising the steps of:providing one or more sources of laser energy that produce laser energy;providing a receiving substrate; wherein the receiving substrate ispositioned opposite the source of laser energy; providing a targetsubstrate; wherein the target substrate is positioned between thereceiving substrate and the source of laser energy; wherein the targetsubstrate comprises a laser-transparent support and a compositematerial; wherein the laser-transparent support has a laser-facingsurface facing the source of laser energy; wherein the laser-transparentsupport has a support surface facing the receiving substrate; whereinthe composite material has a back surface in contact with the supportsurface; wherein the composite material has a front surface facing thereceiving substrate; wherein the composite material comprises acomprises a matrix material and a transfer material; and wherein thematrix material has the property of being desorbed from thelaser-transparent support when exposed to the laser energy; positioningthe source of laser energy in a spaced relation to the target substrateso that the laser energy will strike the composite material at a definedtarget location; positioning the receiving substrate in a spacedrelation to the target substrate; and exposing the target substrate tothe laser energy; wherein the laser energy is directed through thelaser-facing surface and through the laser-transparent support to strikethe composite material at the support surface-back surface interface atthe defined target location; wherein the laser energy has sufficientenergy to cause the desorption of the composite material from thesupport surface; and wherein the desorbed composite material isdeposited at a defined receiving location on the receiving substrate toform a deposited composite material.
 2. The method of claim 1, whereinthe method is controlled by a computer.
 3. The method of claim 1,wherein the steps are carried out at about room temperature; and whereinthe steps are carried out at about atmospheric pressure.
 4. The methodof claim 1, wherein the steps are carried out under one or morecontrolled conditions selected from the group consisting of humidity,atmospheric composition, air pressure, temperature, sterility.
 5. Themethod of claim 1, wherein the source of laser energy is a pulsed laser.6. The method of claim 1, wherein the laser energy is focussed throughan objective.
 7. The method of claim 1, wherein the steps of positioningthe source of laser energy and positioning the receiving substrate areachieved through the use of one or more positioning means selected fromthe group consisting of a laser positioning means, a target substratepositioning means, and a receiving substrate positioning means.
 8. Themethod of claim 1, wherein the steps of positioning the source of laserenergy, positioning the receiving substrate, and exposing the targetsubstrate are repeated at successive defined target locations andsuccessive defined receiving locations; and wherein the compositematerial is deposited in a two-dimensional pattern or athree-dimensional pattern of deposited composite material.
 9. The methodof claim 1 comprising the following additional steps performed beforethe step of providing a target substrate: positioning the receivingsubstrate in a spaced relation to the source of laser energy; andexposing the receiving substrate to the laser energy so that the laserenergy machines away a defined machining location on the receivingsubstrate.
 10. The method of claim 9, wherein the defined machininglocation comprises a via through the receiving substrate.
 11. The methodof claim 9, wherein the composite material is deposited into a definedmachining location that has been previously machined away by the laserenergy.
 12. The method of claim 1 comprising the following additionalsteps after the step of exposing the target substrate: removing thetarget substrate from its position between the source of laser energyand the receiving substrate; positioning the receiving substrate in aspaced relation to the source of laser energy; and exposing thereceiving substrate to the laser energy so that the laser energymachines away a defined machining location on the receiving substrate oron the deposited composite material.
 13. The method of claim 12, whereinthe defined machining location comprises a via through the receivingsubstrate.
 14. The method of claim 1, wherein the step of providing atarget substrate is repeated one or more times using target substratescomprising different composite materials; and wherein the differentcomposite materials are deposited in respective patterns on thereceiving substrate.
 15. The method of claim 14, wherein the differentcomposite materials comprise different transfer materials.
 16. Themethod of claim 14, wherein one or more composite materials comprise amatrix material and an electronic transfer material; and wherein one ormore electronic transfer materials are used to create electroniccircuitry on the receiving substrate.
 17. The method of claim 16,wherein the one or more electronic transfer materials are independentlyselected from the group consisting of metal, dielectric, resist,semiconductor, and combinations thereof.
 18. The method of claim 1,wherein the laser-transparent support comprises quartz or machine etchedquartz.
 19. The method of claim 1, wherein the laser-transparent supportcomprises a laser-transparent flexible polymer ribbon.
 20. The method ofclaim 1, wherein the support surface of the laser-transparent supportcomprises a laser-absorbing layer in contact with the back surface ofthe composite material; and wherein the laser-absorbing layer isvaporized by the laser energy.
 21. The method of claim 20, wherein thelaser-absorbing layer comprises one or more materials selected from thegroup consisting of gold, chrome, and titanium.
 22. The method of claim1, wherein the receiving substrate comprises a non-planar surface. 23.The method of claim 1, wherein the receiving substrate comprises one ormore materials selected from the group consisting of chemicallyfunctionalized glass, polymer-coated glass, quartz, natural hydrogel,synthetic hydrogel, uncoated glass, nitrocellulose coated glass,silicon, glass, plastics, metals, and ceramics.
 24. The method of claim1, wherein the receiving substrate comprises functionalization selectedfrom the group consisting of covalent functionalization, physisorbedfunctionalization, and combinations thereof.
 25. The method of claim 24,wherein the functionalization is selected from the group consisting of aliving host, a living cell, a living cell culture, a non-living cell, anon-living group of cells, a living tissue, a chemically functionalizedsurface, and a biologically functionalized surface.
 26. The method ofclaim 1, wherein the transfer material comprises a biomaterial.
 27. Themethod of claim 26, wherein the biomaterial is living or active.
 28. Themethod of claim 27, wherein the living or active biomaterial remainsliving or active on the receiving substrate.
 29. The method of claim 26,wherein the biomaterial comprises one or more materials selected fromthe group consisting of proteins, hormones, enzymes, antibodies, DNA,portions of DNA strands, inorganic nutrients, aqueous salt solutions,RNA, nucleic acids, aptamers, antigens, lipids, oligopeptides,polypeptides, cofactors, and polysaccharides.
 30. The method of claim26, wherein the biomaterial comprises one or more materials selectedfrom the group consisting of a single cell, groups of cells, livingcells, multi-cell assemblies, pluripotent cells, stem cells, heartcells, lung cells, muscle cells neurons, and neural networks.
 31. Themethod of claim 26, wherein the biomaterial comprises one or morematerials selected from the group consisting of living tissue, skin,hair-producing tissue, nail-producing tissue, and brain tissue.
 32. Themethod of claim 26, wherein the biomaterial comprises one or morematerials selected from the group consisting of DNA-coated particles,protein-coated particles, and RNA-coated particles.
 33. The method ofclaim 26, wherein the biomaterial comprises one or more functionalsupporting media selected from the group consisting of nutrients, andother life supporting material.
 34. The method of claim 26, wherein thebiomaterial comprises one or more tagging compounds selected from thegroup consisting of organic tagging compounds and inorganic taggingcompounds.
 35. The method of claim 26, wherein the composite material isat about the incubation temperature of the biomaterial.
 36. The methodof claim 1, wherein the matrix material comprises one more materialsselected from the group consisting of glycerol, water, polymer, cellmedium, cell nutrient, natural hydrogel, synthetic hydrogel, surfactant,antibiotic, antibody, antigen, protein, dimethylsulfoxide,water/dimethylsulfoxide mixture, agarose, saline solution, dielectricparticles, metal particles, aqueous inorganic salt solution,nitrocellulose gel, sol gel, ceramic composite, DNA-coated particles,protein-coated particles, and RNA-coated particles.
 37. The method ofclaim 1, wherein the matrix material comprises a mixture of water andglycerol.
 38. The method of claim 1, wherein the composite material isfrozen to the laser-transparent support.
 39. The method of claim 1,wherein the composite material is at a temperature of from about −50° C.to about 100° C.
 40. The method of claim 1, wherein the depositedcomposite material is an engineered cellular or composite structures forgrowth, repair, replacement, or improvement of tissue.
 41. The method ofclaim 1, wherein the deposited composite material is a living organ. 42.The method of claim 1, wherein the deposited composite material is adevice to investigate inter- and intracellular signaling.
 43. The methodof claim 1, wherein the deposited composite material is a living deviceto control or divert the flow of fluid through microfluidic channels.44. The method of claim 1, wherein the deposited composite material is aliving, miniature electrode.
 45. The method of claim 1, wherein thedeposited composite material is a neural network.
 46. The method ofclaim 1, wherein the deposited composite material is a device toinvestigate cell aging.
 47. The method of claim 1, wherein the depositedcomposite material is a bridge to connect a nerve synapse.
 48. Themethod of claim 1, wherein the deposited composite material is abiofilm.
 49. The method of claim 1, wherein the deposited compositematerial is a drug delivery system or coating.
 50. The method of claim1, wherein the deposited composite material is an implantable drugdelivery system.
 51. The method of claim 1, wherein the depositedcomposite material is a chemical or biological sensing device to sensechemicals or biomaterials.
 52. The method of claim 1, wherein thedeposited composite material is an implantable, biocompatiblesensor/signaler device.